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Immunoinformatics: The Next Step in Vaccine Design

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Infectious Disease Informatics

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Abstract

T cells have come to be recognized as critical mediators of competent and lasting responses elicited by vaccines. This recognition catalyzed the development of computer-driven (immunoinformatics) methods for defining T-cell epitopes directly from protein sequences. Subsequently, investigations into the role of effector and regulatory T cells have leapfrogged directly from genome and protein sequences to the leading edge of immunology and vaccine research. Although immunoinformatics tools have been available for over a decade, recent technological advances have led to significant improvements in the tools, raising their level of accuracy and increasing their utility in the design of effective T-cell epitope-driven vaccines. Additional technical advances in the field of vaccine delivery and adjuvants have led to significant success at the preclinical level of vaccine design. These advances have the potential to reduce the lead time for vaccines to enter the clinic. Epitope-based vaccines have significant advantages in terms of their safety profile since they are composed of antigen specific sequences. The vaccine contains fewer cross-reactive epitopes than the whole pathogen would, which lowers regulatory hurdles and hastens approval by regulatory agencies. In this chapter, we review recent advances that will accelerate T-cell epitope-driven vaccine development, and provide three examples of successful preclinical epitope-driven vaccine studies: (1) a vaccine that eradicates Helicobacter pylori infection, (2) a candidate smallpox vaccine that affords protection against vaccinia, and (3) a vaccine against tularemia. Owing to recent improvements in vaccine design and delivery systems, now few obstacles remain in the path of a new generation of T-cell epitope-driven vaccines.

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References

  • Albert ML, Jegathesan M, Darnell RB (2001) Dendritic cell maturation is required for the cross-tolerization of CD8 + T cells. Nat Immunol 2(11):1010–1017

    CAS  PubMed  Google Scholar 

  • Ardito M (2009) Manuscript in preparation (PDF of poster, available at www.EpiVax.com)

    Google Scholar 

  • Asjö B, Stavang H, Sørensen B, Baksaas I et al (2002) Phase I trial of a therapeutic HIV type 1 vaccine, Vacc-4x, in HIV type 1-infected individuals with or without antiretroviral therapy. AIDS Res Hum Retroviruses 18:1357–1365

    PubMed  Google Scholar 

  • Belz GT, Wodarz D, Diaz G et al (2002) Compromised influenza virus-specific CD8(+)-T-cell memory in CD4(+)-T-cell-deficient mice. J Virol 76(23):12388–12393

    CAS  PubMed  Google Scholar 

  • Bendelac A, Medzhitov R (2002) Adjuvants of immunity: harnessing innate immunity to promote adaptive immunity. J Exp Med 195:F19–F23

    CAS  PubMed  Google Scholar 

  • Blattman JN, Sourdive DJ, Murali-Krishna K et al (2000) Evolution of the T-cell repertoire during primary, memory, and recall responses to viral infection. J Immunol 165(11):6081–6090

    CAS  PubMed  Google Scholar 

  • Bond KB, Sriwanthana B, Hodge TW et al (2001) An HLA-directed molecular and bioinformatics approach identifies new HLA-A11 HIV-1 subtype E cytotoxic T lymphocyte epitopes in HIV-1-infected Thais. AIDS Res Hum Retroviruses 20:703–717

    Google Scholar 

  • Bonifaz LC, Bonnyay DP, Mahnke K et al (2002) Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8 + T cell tolerance. J Exp Med 196:1627–1638

    CAS  PubMed  Google Scholar 

  • Boscardin SB, Hafalla JC, Masilamani RF et al (2006) Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses. J Exp Med 203(3):599–606

    CAS  PubMed  Google Scholar 

  • Bruder D, Westendorf AM, Hansen W, Prettin S et al (2005) On the edge of autoimmunity: T-cell stimulation by steady-state dendritic cells prevents autoimmune diabetes. Diabetes 54(12):3395–3401

    CAS  PubMed  Google Scholar 

  • Canaday DH, Wilkinson RJ, Li Q et al (2001) CD4(+) and CD8(+) T cells kill intracellular Mycobacterium tuberculosis by a perforin and Fas/Fas ligand-independent mechanism. J Immunol 167:2734–2742

    CAS  PubMed  Google Scholar 

  • Caux C, Massacrier C, Vanbervliet B et al (1994) Activation of human dendritic cells through CD40 cross linking. J Exp Med 180:1263–1272

    CAS  PubMed  Google Scholar 

  • Chen L, Wang J, Zganiacz A, Xing Z (2004) Single intranasal mucosal Mycobacterium bovis BCG vaccination confers improved protection compared to subcutaneous vaccination against pulmonary tuberculosis. Infect Immun 72(1):238–246

    CAS  PubMed  Google Scholar 

  • Cho S, Mehra V, Thoma-Uszynski S et al (2000) Antimicrobial activity of MHC Class I-restricted CD8 + T cells in human tuberculosis. P Natl Acad Sci USA 97:12210–12215

    CAS  Google Scholar 

  • Cooper AM, Dalton DK, Stewart TA et al (1993) Disseminated tuberculosis in interferon gamma gene-disrupted mice. J Exp Med 178:2243–2247

    CAS  PubMed  Google Scholar 

  • De Groot AS, Berzofsky JA (2004) From genome to vaccine – new immunoinformatics tools for vaccine design. Methods 34:425–428

    PubMed  Google Scholar 

  • De Groot AS, Jesdale BM, Szu E et al (1997) An interactive Web site providing major histocompatibility ligand predictions: application to HIV research. AIDS Res Hum Retroviruses 13:529–531

    PubMed  Google Scholar 

  • De Groot AS, Bosma A, Chinai N et al (2001) From genome to vaccine: in silico predictions, ex vivo verification. Vaccine 19(31):4385–4395

    PubMed  Google Scholar 

  • De Groot AS et al (2007) Immunomics Reviews, vol 1. Springer, NY

    Google Scholar 

  • De Groot AS, Knopf PM, Rivera D, Martin W (2007) Immunoinformatics applied to modifying and improving biological therapeutics. In: Schönbach C, Ranganathan S, Brusic V (eds) Immunoinformatics (Immunoinfomatics Reviews), Kluwer publications 1:109–132. ISBN: 978-0-387-72967-1

    Google Scholar 

  • De Groot AS, McMurry J, Moise L, Martin B (2008) Immunome-derived vaccines. In: Falus Falus A (ed) Springer immunomics series, Series: 2, vol. 1. Kluwer publications. Immunomics Reviews, Submitted, 2008

    Google Scholar 

  • DeLeo AB, Whiteside TL (2008) Development of multi-epitope vaccines targeting wild-type sequence p53 peptides. Expert Rev Vaccines 7(7):1031–1040

    CAS  PubMed  Google Scholar 

  • Dietrich J, Andersen C, Rappuoli R, Doherty TM, Jensen CG, Andersen P (2006) Mucosal administration of Ag85B-ESAT-6 protects against infection with Mycobacterium tuberculosis and boosts prior bacillus Calmette-Guerin immunity. J Immunol 177(9):6353–6360

    CAS  PubMed  Google Scholar 

  • Dong Y, Demaria S, Sun X et al (2004) HLA-A2-restricted CD8 + -cytotoxic- T cell responses to novel epitopes in Mycobacterium tuberculosis superoxide dismutase, alanine dehydrogenase, and glutamine synthetase. Infect Immun 72:2412–2415

    CAS  PubMed  Google Scholar 

  • Doolan DL, Hoffman SL, Southwood S et al (1997) Degenerate cytotoxic T-cell epitopes from P. Falciparum restricted by multiple HLA-A and HLA-B supertype alleles. Immunity 7(1):97–112

    CAS  PubMed  Google Scholar 

  • Duraiswamy et al (2003) Therapeutic LMP1 Polyepitope Vaccine for EBV-associated Hodgkin Disease and Nasopharyngeal Carcinoma. Blood 101(8):3150–3156

    CAS  PubMed  Google Scholar 

  • Elliott SL, Suhrbier A, Miles JJ, Lawrence G et al (2008) Phase I trial of a CD8 + T-cell peptide epitope-based vaccine for infectious mononucleosis. J Virol 82:1448–1457

    CAS  PubMed  Google Scholar 

  • Falugi F, Petracca R, Mariani M, Luzzi E et al (2001) Rationally designed strings of promiscuous CD4(+) T-cell epitopes provide help to Haemophilus influenzae type b oligosaccharide: a model for new conjugate vaccines. Eur J Immunol 31(12):3816–3824

    CAS  PubMed  Google Scholar 

  • Fan XJ, Chua A, Shahi CN, McDevitt J, Keeling PW, Kelleher D (1994) Gastric T lymphocyte responses to Helicobacter pylori in patients with H.pylori colonisation. Gut 35(10):1379–1384

    CAS  PubMed  Google Scholar 

  • Flynn JL, Chan J, Triebold KJ et al (1993) An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med 178:2249–2254

    CAS  PubMed  Google Scholar 

  • Fraser CK, Diener KR, Brown MP, Hayball JD (2007) Improving vaccines by incorporating immunological coadjuvants. Expert Rev Vaccines 6:559–578

    CAS  PubMed  Google Scholar 

  • Fujii S, Liu K, Smith C et al (2004) The linkage of innate to adaptive immunity via maturing dendritic cells in vivo requires CD40 ligation in addition to antigen presentation and CD80/86 costimulation. J Exp Med 199(12):1607–1618

    CAS  PubMed  Google Scholar 

  • Gahery H, Daniel N, Charmeteau B, Ourth L et al (2006) New CD4 + and CD8 + T-cell responses induced in chronically HIV type-1-infected patients after immunizations with an HIV type 1 lipopeptide vaccine. AIDS Res Hum Retroviruses 22:684–694

    CAS  PubMed  Google Scholar 

  • Ghosh S, Pal S, Das S, Dasgupta SK, Majumdar S (1998) Lipoarabinomannan induced cytotoxic effects in human mononuclear cells. FEMS Immunol Med Microbiol 21:181–188

    CAS  PubMed  Google Scholar 

  • Gianfrani C, Oseroff C, Sidney J et al (2000) Human memory CTL response specific for influenza A virus is broad and multispecific. Hum Immunol 61:438–452

    CAS  PubMed  Google Scholar 

  • Gil H, Platz GJ, Forestal CA, Monfett M et al (2006) Deletion of TolC orthologs in Francisella tularensis identifies roles in multidrug resistance and virulence. Proc Natl Acad Sci USA 103(34):12897–12902

    CAS  PubMed  Google Scholar 

  • Gillespie GM, Wills MR, Appay V et al (2000) Functional heterogeneity and high frequencies of cytomegalovirus-specific CD8(+) T lymphocytes in healthy seropositive donors. J Virol 74:8140–8150

    CAS  PubMed  Google Scholar 

  • Giri PK, Sable SB, Verma I, Khuller GK (2005) Comparative evaluation of intranasal and subcutaneous route of immunization for development of mucosal vaccine against experimental tuberculosis. FEMS Immunol Med Microbiol 45(1):87–93

    CAS  PubMed  Google Scholar 

  • Gregory SH, Mott S, Phung J, Lee J, Moise L et al (2008) Epitope-based vaccination against pneumonic tularemia (Manuscript submitted to Vaccine)

    Google Scholar 

  • Gursel I, Gursel M, Ishii KJ, Klinman DM (2001) Sterically stabilized cationic liposomes improve the uptake and immunostimulatory activity of CpG oligonucleotides. J Immunol 167(6):3324–3328

    CAS  PubMed  Google Scholar 

  • Hanke T (2008) STEP trial and HIV-1 vaccines inducing T-cell responses. Expert Rev Vaccines 7(3):303–309

    CAS  PubMed  Google Scholar 

  • Harrer T, Harrer E, Kalams SA et al (1996) Cytotoxic T-lymphocytes in asymptomatic long-term nonprogressing HIV-1 infection. Breadth and specificity of the response and relation to in vivo viral quasispecies in a person with prolonged infection and low viral load. J Immunol 156(7):2616–2623

    CAS  PubMed  Google Scholar 

  • Hawiger D, Inaba K, Dorsett Y et al (2001) Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J Exp Med 194(6):769–779

    CAS  PubMed  Google Scholar 

  • Janeway CA Jr, Medzhitov R (2002) Innate immune recognition. Annu Rev Immunol 20:197–216

    CAS  PubMed  Google Scholar 

  • Jiang W, Swiggard WJ, Heufler C et al (1995) The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing. Nature 375:151–155

    CAS  PubMed  Google Scholar 

  • Johansson BE, Moran TM, Kilbourne ED (1987) Antigen-presenting B cells and helper T cells cooperatively mediate intravirionic antigenic competition between influenza A virus surface glycoproteins. Proc Natl Acad Sci USA 84(19):6869–6873

    CAS  PubMed  Google Scholar 

  • Kamperschroer C, Dibble JP, Meents DL et al (2006) SAP is required for TH cell function and for immunity to influenza. J Immunol 177:5317–5327

    CAS  PubMed  Google Scholar 

  • Kaufmann SH, Hess J (1999) Impact of intracellular location of and antigen display by intracellular bacteria, implications for vaccine development. Immunol Lett 65:81–84

    CAS  PubMed  Google Scholar 

  • Koita OA, Dabitao D, Mahamadou I et al (2006) Confirmation of immunogenic consensus sequence HIV-1 T-cell epitopes in Bamako, Mali and Providence, RI. Hum Vaccin 2(3):119–128

    CAS  PubMed  Google Scholar 

  • Koren E, De Groot AS, Jawa V et al (2007) Clinical validation of the “in silico” prediction of immunogenicity of a human recombinant therapeutic protein. Clin Immunol 124(1):26–32

    CAS  PubMed  Google Scholar 

  • Kran AM, Sørensen B, Nyhus J, Sommerfelt MA et al (2004) HLA- and dose-dependent immunogenicity of a peptide-based HIV-1 immunotherapy candidate (Vacc-4x). AIDS 18:1875–1883

    CAS  PubMed  Google Scholar 

  • Kretschmer K, Apostolou I, Hawiger D, Khazaie K et al (2005) Inducing and expanding regulatory T cell populations by foreign antigen. Nat Immunol 6(12):1219–1227

    CAS  PubMed  Google Scholar 

  • Krieg AM, Yi AK, Schorr J, Davis HL (1998) The role of CpG dinucleotides in DNA vaccines. Trends Microbiol 6:23–27

    CAS  PubMed  Google Scholar 

  • Kuchroo VK, Das MP, Brown JA, Ranger AM et al (1995) B7–1 and B7–2 costimulatory molecule activate differentially the TH1/TH2 developmental pathways: application to autoimmune disease therapy. Cell 80:707–718

    CAS  PubMed  Google Scholar 

  • Kuzushita N, Rogers AB, Monti NA, Whary MT et al (2005) p27kip1 deficiency confers susceptibility to gastric carcinogenesis in Helicobacter pylori-infected mice. Gastroenterol 129(5):1544–1556

    CAS  Google Scholar 

  • Lazarski CA, Chaves FA, Jenks SA et al (2005) The kinetic stability of MHC class II:peptide complexes is a key parameter that dictates immunodominance. Immun 23(1):29–40

    CAS  Google Scholar 

  • Lefford MJ (1975) Transfer of adoptive immunity to tuberculosis in mice. Infect Immun 11:1174–1181

    CAS  PubMed  Google Scholar 

  • Lewinsohn DA, Winata E, Swarbrick GM et al (2007) Immunodominant tuberculosis CD8 antigens preferentially restricted by HLA-B. PLoS Pathog 3(9):1240–1249

    CAS  PubMed  Google Scholar 

  • Luft T, Jefford M, Luetjens P, Toy T et al (2002) Functionally distinct dendritic cell (DC) populations induced by physiologic stimuli: prostaglandin E(2) regulates the migratory capacity of specific DC subsets. Blood 100:1362–1372

    CAS  PubMed  Google Scholar 

  • Mahnke K, Enk AH (2005) Dendritic cells: key cells for the induction of regulatory T cells? Curr Top Microbiol Immunol 293:133–150

    CAS  PubMed  Google Scholar 

  • Mahnke K, Guo M, Lee S et al (2000) The dendritic cell receptor for endocytosis, DEC-205, can recycle and enhance antigen presentation via major histocompatibility complex class II – positive lysosomal compartments. J Cell Biol 151:673–683

    CAS  PubMed  Google Scholar 

  • Mahnke K, Qian Y, Knop J, Enk AH (2003) Induction of CD4 +/CD25 + regulatory T cells by targeting of antigens to immature dendritic cells. Blood 101(12):4862–4869

    CAS  PubMed  Google Scholar 

  • Marshall D, Sealy R, Sangster M, et al (1999) TH cells primed during influenza virus infection provide help for qualitatively distinct antibody responses to subsequent immunization. J Immunol 163:4673–4682

    CAS  PubMed  Google Scholar 

  • Mayerova D, Parke EA, Bursch LS et al (2004) Langerhans cells activate naive self-antigen-specific CD8 T cells in the steady state. Immun 21(3):391–400

    CAS  Google Scholar 

  • McElrath MJ, De Rosa SC, Moodie Z et al (2008) HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis. Lancet 372(9653):1894–1905

    CAS  PubMed  Google Scholar 

  • McMurry J, Sbai H, Gennaro ML et al (2005) Analyzing Mycobacterium tuberculosis proteomes for candidate vaccine epitopes. Tuberculosis 85:95–105

    CAS  PubMed  Google Scholar 

  • McMurry JA, Johansson BE, De Groot AS (2008) A call to cellular & humoral arms: enlisting cognate T cell help to develop broad-spectrum vaccines against influenza. A Hum Vaccin 4(2):148–157

    CAS  Google Scholar 

  • Menges M, Rossner S, Voigtlander C et al (2002) Repetitive injections of dendritic cells matured with tumor necrosis factor alpha induce antigen-specific protection of mice from autoimmunity. J Exp Med 195(1):15–21

    CAS  PubMed  Google Scholar 

  • Munz C, Steinman RM, Fujii S (2005) Dendritic cell maturation by innate lymphocytes: coordinated stimulation of innate and adaptive immunity. J Exp Med 202(2):203–207

    PubMed  Google Scholar 

  • Nara PL, Lin G. (2005) HIV-1: the confounding variables of virus neutralization. Curr Drug Targets Infect Disord 5(2):157–170

    CAS  PubMed  Google Scholar 

  • Naz RK. Status of contraceptive vaccines. Am J Reprod Immunol. 2009 61(1):11–18

    PubMed  Google Scholar 

  • Ostrowski M, Galeota JA, Jar AM et al (2002) Identification of neutralizing and nonneutralizing epitopes in the porcine reproductive and respiratory syndrome virus GP5 ectodomain. J Virol 76(9):4241–4250 Erratum in 2002 J Virol 76(13):6863

    CAS  Google Scholar 

  • Ozpolat B, Actor JK, Rao XM, Lee S et al (2000) Quantitation of Helicobacter pylori in the stomach using quantitative polymerase chain reaction assays. Helicobacter 5(1):13–21

    CAS  PubMed  Google Scholar 

  • Petrovsky N, Brusic V (2006) Bioinformatics for study of autoimmunity. Autoimmunity 39(8):635–643

    CAS  PubMed  Google Scholar 

  • Pietersz GA, Pouniotis DS, Apostolopoulos V (2006) Design of peptide-based vaccines for cancer. Curr Med Chem 13:1591–1607

    CAS  PubMed  Google Scholar 

  • Quiding-Järbrink M, Lundin BS, Lönroth H, Svennerholm AM (2001) CD4 + and CD8 + T cell responses in Helicobacter pylori-infected individuals. Clin Exp Immunol 123(1):81–87

    PubMed  Google Scholar 

  • Rasmussen IB, Lunde E, Michaelsen TE et al (2001) The principle of delivery of T cell epitopes to antigen-presenting cells applied to peptides from influenza virus, ovalbumin, and hen egg lysozyme: implications for peptide vaccination. Proc Natl Acad Sci USA 98:10296–10301

    CAS  PubMed  Google Scholar 

  • Reis e Sousa C (2006) Dendritic cells in a mature age. Nat Rev Immunol 6(6):476–483

    CAS  PubMed  Google Scholar 

  • Rupnow MF, Shachter RD, Owens DK, Parsonnet J (2001) Quantifying the population impact of a prophylactic Helicobacter pylori vaccine. Vaccine 20(5–6):879–885

    CAS  PubMed  Google Scholar 

  • Russell SM, Liew FY (1979) T cells primed by influenza virion internal components can cooperate in the antibody response to haemagglutinin. Nature 280(5718):147–148

    CAS  PubMed  Google Scholar 

  • Santosuosso M, McCormick S, Zhang X, Zganiacz A, Xing Z (2006) Intranasal boosting with an adenovirus-vectored vaccine markedly enhances protection by parenteral Mycobacterium bovis BCG immunization against pulmonary tuberculosis. Infect Immun 74(8):4634–4643

    CAS  PubMed  Google Scholar 

  • Santra S, Barouch DH, Kuroda MJ et al (2002) Prior vaccination increases the epitopic breadth of the cytotoxic T-lymphocyte response that evolves in rhesus monkeys following a simian-human immunodeficiency virus infection. J Virol 76(12):6376–6381

    CAS  PubMed  Google Scholar 

  • Scandella E, Men Y, Gillessen S, Forster R, Groettrup M (2002) Prostaglandin E2 is a key factor for CCR7 surface expression and migration of monocyte-derived dendritic cells. Blood 100:1354–1361

    CAS  PubMed  Google Scholar 

  • Scanga CA, Mohan VP, Yu K et al (2000) Depletion of CD4(+)T cells causes reactivation of murine persistent tuberculosis despite continued expression of interferon gamma and nitric oxide synthase 2. J Exp Med 192:347–358

    CAS  PubMed  Google Scholar 

  • Scheinecker C, McHugh R, Shevach EM et al (2002) Constitutive presentation of a natural tissue autoantigen exclusively by dendritic cells in the draining lymph node. J Exp Med 196(8):1079–1090

    CAS  PubMed  Google Scholar 

  • Scherle PA, Gerhard W (1986) Functional analysis of influenza-specific helper T cell clones in vivo. T cells specific for internal viral proteins provide cognate help for B cell responses to hemagglutinin. J Exp Med 164(4):1114–1128

    CAS  PubMed  Google Scholar 

  • Scherle PA, Gerhard W (1988) Differential ability of B cells specific for external vs. internal influenza virus proteins to respond to help from influenza virus-specific T-cell clones in vivo. Proc Natl Acad Sci USA 85(12):4446–4450

    CAS  PubMed  Google Scholar 

  • Seder RA, Darrah PA, Roederer M (2008) T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol 8(4):247–258

    CAS  PubMed  Google Scholar 

  • Sen G, Chen Q, Snapper CM (2006) Immunization of aged mice with a pneumococcal conjugate vaccine combined with an unmethylated CpG-containing oligodeoxynucleotide restores defective immunoglobulin G antipolysaccharide responses and specific CD4 + -T-cell priming to young adult levels. Infect Immun 74(4):2177–2186

    CAS  PubMed  Google Scholar 

  • Serbina NV, Flynn JL (2001) CD8(+).T cells participate in the memory immune response to Mycobacterium tuberculosis. Infect Immun 69:4320–4328

    CAS  PubMed  Google Scholar 

  • Shahinian A, Pfeffer K, Lee KP, Kundig TM et al (1993) Differential T-cell costimulatory requirements in CD28-deficient mice. Science 261:609–612

    CAS  PubMed  Google Scholar 

  • Shibaki A, Sato A, Vogel JC et al (2004) Induction of GVHD-like skin disease by passively transferred CD8(+) T-cell receptor transgenic T cells into keratin 14-ovalbumin transgenic mice. J Invest Dermatol 123(1):109–115

    CAS  PubMed  Google Scholar 

  • Spörri R, Reis e Sousa C (2005) Inflammatory mediators are insufficient for full dendritic cell activation and promote expansion of CD4 + T cell populations lacking helper function. Nat Immunol 6(2):163–170

    PubMed  Google Scholar 

  • Steinman RM (2001) Dendritic cells and the control of immunity: enhancing the efficiency of antigen presentation. Mt Sinai J Med 68:160–166

    CAS  PubMed  Google Scholar 

  • Subbramanian RA, Kuroda MJ, Charini WA et al (2003) Magnitude and diversity of cytotoxic-T-lymphocyte responses elicited by multiepitope DNA vaccination in rhesus monkeys. J Virol 77(18):10113–10118

    CAS  PubMed  Google Scholar 

  • Takeda K, Kaisho T, Akira S (2003) Toll-like receptors. Ann Rev Immunol 21:335–376

    CAS  Google Scholar 

  • Tatarewicz SM, Wei X, Gupta S et al (2007) Development of a maturing T-cell-mediated immune response in patients with idiopathic Parkinson’s disease receiving r-metHuGDNF via continuous intraputaminal infusion. J Clin Immunol 27(6):620–627

    PubMed  Google Scholar 

  • Thurmond J, Yoon H, Kuiken C et al (2008) Web-based design and evaluation of T-cell vaccine candidates. Bioinform 24(14):1639–1640

    CAS  Google Scholar 

  • Tian L, Wang HN, Lu D, Zhang YF, Wang T, Kang RM (2008) The immunoreactivity of a chimeric multi-epitope DNA vaccine against IBV in chickens. Biochem Biophys Res Commun 2008 377(1) 221–225

    CAS  PubMed  Google Scholar 

  • Trumpfheller C, Finke JS, Lopez CB et al (2006) Intensified and protective CD4 + T cell immunity in mice with anti-dendritic cell HIV gag fusion antibody vaccine. J Exp Med 203(3):607–617

    CAS  PubMed  Google Scholar 

  • Vollmer J (2005) Progress in drug development of immunostimulatory CpG oligodeoxynucleotide ligands for TLR9.Expert Opin Biol Ther 5(5):673–682

    CAS  PubMed  Google Scholar 

  • Wang D, Liebowitz D, Kieff E. (1985) An Epstein-Barr virus membrane protein expressed in immortalized lymphocytes transforms established rodent cells. Cell 43:831–840

    CAS  PubMed  Google Scholar 

  • Wang J, Thorson L, Stokes RW, Santosuosso M et al (2004) Single mucosal, but not parenteral, immunization with recombinant adenoviral-based vaccine provides potent protection from pulmonary tuberculosis. J Immunol 173(10):6357–6365

    CAS  PubMed  Google Scholar 

  • Wilson CC, Newman MJ, Livingston BD et al (2008) Clinical phase 1 testing of the safety and immunogenicity of an epitope-based DNA vaccine in human immunodeficiency virus type 1-infected subjects receiving highly active antiretroviral therapy. Clin Vaccine Immunol 15(6):986–994

    CAS  PubMed  Google Scholar 

  • Zhang Q, Wang P, Kim Y et al (2008) Immune epitope database analysis resource (IEDB-AR). Nucleic Acids Res 36:W513–W518

    CAS  PubMed  Google Scholar 

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  1. Brown University, School of Medicine, Providence, RI, USA

    Tobias Cohen, Lenny Moise, William Martin & Anne S. De Groot

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  2. Lenny Moise
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  1. Sydney Medical School, University of Sydney, Sydney, 2006, Australia

    Vitali Sintchenko

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Cohen, T., Moise, L., Martin, W., De Groot, A.S. (2010). Immunoinformatics: The Next Step in Vaccine Design. In: Sintchenko, V. (eds) Infectious Disease Informatics. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1327-2_11

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